Methods were developed for the determination of cAMP, cGMP, gamma-aminobutyric acid, substance P and endogenous opiate ligands. Using these methods, it is possible to measure these compounds in a variety of tissues and under many physiological conditions. In particular, all of the above compounds have been or are being measured in cerebrospinal fluid from human subjects. With the available cerebrospinal fluid from patients under study in the Sections of Psychobiology and Neuropsychopharmacology, no differences between patients with schizophrenia and affective disorders could be demonstrated for cAMP, cGMP and GABA.